ChIP-Atlas 3.0: a data-mining suite to explore chromosome architecture together with large-scale regulome data

Abstract

ChIP-Atlas (https://chip-atlas.org/) presents a suite of data-mining tools for analyzing epigenomic landscapes, powered by the comprehensive integration of over 376 000 public ChIP-seq, ATAC-seq, DNase-seq and Bisulfite-seq experiments from six representative model organisms. To unravel the intricacies of chromatin architecture that mediates the regulome-initiated generation of transcriptional and phenotypic diversity within cells, we report ChIP-Atlas 3.0 that enhances clarity by incorporating additional tracks for genomic and epigenomic features within a newly consolidated 'annotation track' section. The tracks include chromosomal conformation (Hi-C and eQTL datasets), transcriptional regulatory elements (ChromHMM and FANTOM5 enhancers), and genomic variants associated with diseases and phenotypes (GWAS SNPs and ClinVar variants). These annotation tracks are easily accessible alongside other experimental tracks, facilitating better elucidation of chromatin architecture underlying the diversification of transcriptional and phenotypic traits. Furthermore, 'Diff Analysis,' a new online tool, compares the query epigenome data to identify differentially bound, accessible, and methylated regions using ChIP-seq, ATAC-seq and DNase-seq, and Bisulfite-seq datasets, respectively. The integration of annotation tracks and the Diff Analysis tool, coupled with continuous data expansion, renders ChIP-Atlas 3.0 a robust resource for mining the landscape of transcriptional regulatory mechanisms, thereby offering valuable perspectives, particularly for genetic disease research and drug discovery.

Graphical Abstract

Figure 1.

Example for browsing annotation tracks in ChIP-Atlas 3.0. Peak-call data for TF and histone ChIP-seq (ChIP-Atlas 1.0), ATAC-seq and Bisulfite-seq experiments (ChIP-Atlas 2.0), along with ChromHMM, eQTL and GWAS SNPs tracks (ChIP-Atlas 3.0) in human (hg38) blood around the PELATON locus are shown in the IGV genome browser. Panels a, c, e and f show single views of individual alignment data from ChIP-seq, ATAC-seq and Bisulfite-seq experiments (a, IKZF1 ChIP-seq in GM12878 [SRX2424550]; c, H3K27ac ChIP-seq in lymphoblastoid cell line [SRX4288387]; e, ATAC-seq in CD8⁺ T cells [SRX16731555]; g, methylation level in B cells [SRX9500396]) (see the tutorial PDF of Peak Browser [https://chip-atlas.dbcls.jp/data/manual/Peak_Browser/Peak_Browser.pdf] for more information on loading individual data for single views). Panels b, d, f and h show integrative views of TF (b) and histone (d) ChIP-seq peaks, ATAC-seq peaks (f) and hypo-, hyper- and partially methylated regions (h) in the cells categorized as ‘blood’ cell type class. The highlighted region (in gray) indicates an accessible chromatin and hypomethylated region. Bars in panels b, d and f represent the peak regions, the color of which indicates MACS2 scores (–10 × log₁₀[Q-value]); i.e. if MACS2 scores are 50, 500 or over 1000, then the colors are blue, green or red, respectively. Panel h is shown in squished mode, and black, pink and beige bars indicate hyper-, hypo- and partially methylated regions, respectively. Colored bars in panel i indicate various chromatin states. Arrows from short bars to long bars in panel j indicate the effect of gene polymorphisms (short bars) on gene expression (long bars). Bars in panel k represent SNPs associated to diseases, phenotypes, measurements and drug responses. See Supplementary Figure S2A and B for details on the procedures for visualizing these tracks.

Figure 2.

Example of visualizing the results of Diff Analysis tools. (A, B) Screenshot of IGV displaying the returned XML sessions containing alignment data of the query experiments along with the output DARs (A) and DMRs (B). The ‘DARs’ and ‘DMRs’ panels are shown in expanded mode. (A) Bars in the ‘DAR’ panel indicate ES cell- (orange) and myoblast-specific peaks (blue). (B) Bars in the ‘DMR’ panel indicate brain- (orange) and T cell-specific methylated regions (blue). DAR, differentially accessible region; DMR, differentially methylated region. Downloaded results for (A) and (B) are provided in Supplementary Materials S3 and S4, while details on the procedures for performing Diff Analysis are in Supplementary Figure S2C and D.